Arcane items of medical obscurity are the neurologist's lifeblood. We can figure stuff out. This blogger is interested in diseases that affect people-- go somewhere else for results of rat research. Information is meant to be advanced but clinically relevant esoterica.

Sunday, February 14, 2010

Autosomal dominant ataxias with known causation

SCA I--*-- begins as gait disorder, progresses to four extremity ataxia with dysarthria leaving patient wheelchair bound within 15-20 years.There is phenotypic variability and anticipation (genetically). Clinically there is involvement of cerebellum with neuronal dropout of Purkinje cell layer and clinical involvement of the brainstem. No supratentotial involvement. Not as common as type II but well worked out molecularly,

SCA II--*--characterized by ataxia, dysarthria, slow saccades and neuropathy. Originally Cuban description. Very common worldwide, especially in India. Slow saccades are not pathognomonic, they also are seen in SCA I and III. Dementia, areflexia, myokymia also are seen. Gene expansion includes cytoplasmic protein ataxin, function of which is unknown. Anticipation is marked, and disease may present in one generation in old age, in the next much earlier. Number of repeats are 35-77 , with 32-34 "zone of reduced penetrance."

SCA VI --*-- milder disease, pure cerebellar associated with normal lifespan. Presentation is gaze evoked nystagmus, dysarthria, onset at age 50 or so, impaired vibratory and position sense.Its fairly common in Japan and in Germany. Caused by expansion/repeat in voltage dependent calcium channel,same gene that causes episodic ataxia type 2 and familial hemiplegic migraine. However, mutations in these conditions in the same gene are different mutations.

SCA 7--*-- cerebellar brainstem disease associated with retinal degeneration and blindness. It has striking instability of transmission especially with paternal transmission, with cases in utero and in childhood.

DRPLA-- *-- progressive ataxia, choreoathetosis, dementia, seizures, myoclonus, and dystonia. Before age 20 there are almost always seizures and a progressive myoclonic seizure like presentation. Older patients get ataxia with choreoathetosis and dementia. More common in Japan, but Haw River phenotype is an African American family in the Carolinas with seizures and cerebral calcifications.

episodic ataxias--EA1 and EA2 are due to mutations in K and Ca channel genes. EA1-- patients ahve minutes of ataxia due to stress, exercise or change in posture. Patients also may have myokymia. KCNA1 gene. EA2 has ataxia that lasts days , precipitated by stress, exercise or fatigue and is due to mutation of same gene as SCA 6 (CACNA1A4 gene). Acetozolamide may help. Other EA's with prominent vertigo also are described.